Cheap and Efficient Protocol for the Synthesis of Tetrahydroquinazolinone, Dihydropyrimidinone, and Pyrimidinone Derivatives

Abstract

The article reports a practical, simple, and inexpensive procedure for the synthesis of tetrahydroquinazolinone and dihydropyrimidinone derivatives from aldehydes, cyclic ketones, and urea using a catalytic amount of ammonium chloride or lithium perchlorate. The protocol provides good yields and simple workup procedure for the products. By this method, we have prepared and characterized the 4-aryl-3,4,5,6-tetrahydrobenzo[h]quinazolin-2(1H)-one (3a, c, d, f, g, j, k), 4-aryl-3,4-dihydro-1H-indeno[1,2-d]pyrimidin-2(5H)-one (3b, e, h, i), 4-aryl-5,6-dihydrobenzo[h]quinazolin-2(3H)-one (3j′, k′, l′), and 4-aryl-3,5-dihydro-2H-indeno[1,2-d]pyrimidin-2-one (3i′, m′, n′, o′, p′) derivatives. Furthermore, we have synthesized the pyrimidinone derivatives (6a′–e′) using a catalytic amount of cupric chloride from aldehydes, acyclic ketones and urea. The tautomeric interconversion of pyrimidinone derivatives 6a′–e′ ↔ 6a″–e″ has been observed.

Keywords:

• Ammonium chloride
• cupric chloride
• dihydropyrimidinone derivatives
• lithium perchlorate
• pyrimidinone derivatives
• tetrahydroquinazolinone derivatives

Notes

^a Reaction conditions: aldehyde 2 mmol, α-tetralone or 1-indanone 2 mmol, urea 3 mmol, TMSCl 2 mmol, NH₄Cl 50 mol% or LiClO₄ 20% w/w aldehyde, 10 mL CH₃CN, reflux 6h.

^b The number between the parentheses shows the ratio of the nonoxidized to oxidized products.

^c Isolated yield using NH₄Cl catalyst; the number between the parentheses shows the yield using LiClO₄ catalyst.

^a Reaction conditions: aldehyde 2 mmol, acetophenone or 4-methoxy acetophenone 2 mmol, urea 3 mmol, TMSCl 2 mmol, CuCl₂ 10 mol%, 10 mL CH₃CN, reflux 8 h.

^b Isolated yield.